Thalassemias

Question 1

What are thalassemias?

Answer 1

These are genetic diseasses of unbalanced Hb synthesis, with underprodution or no production of one globin chain. Unmatched globins precipitate, damaging RBC membranes, causing their haemolysis while still in the marrow.

Question 2

What are the main types of thalassemia?

Answer 2

• Alpha thalassemia - reduced alpha chain synthesis
• Beta Thalassemia - reduced beta chain synthesis

Question 3

What is the main issue in Beta thalassemia?

Answer 3

Homozygous β-thalassaemia - either no normal β chains are produced (β0) or β-chain production is very reduced (β+). There is an excess of α chains, which precipitate in erythroblasts and red cells causing ineffective erythropoiesis and haemolysis. The excess α chains combine with whatever β, δ and γ chains are produced, resulting in increased quantities of HbA2 and HbF and, at best, small amounts of HbA.

Heterozygous β-thalassaemia - usually symptomless microcytosis with or without mild anaemia.

Question 4

What are the main genetic defects involved in beta thalassemia?

Answer 4

Mainly point mutations rather than gene deletions

Question 5

How is beta thalassemia subdivided clinically?

Answer 5

• Thalassaemia minor
• Thalassaemia intermedia
• Thalassaemia major

Question 6

What are features of beta thalassemia minor?

Answer 6

• Asymptomatic
• Mild hypochromic microcytic anaemia

Question 7

What are features of beta thalassemia intermedia?

Answer 7

• Moderate anaemia - not requiring transfusion
• Splenomegaly
• Boney deformity

Question 8

What are clinical features of B-thalassemia Major?

Answer 8

Presents in 1st year

• Severe anaemia
• Recurrent bacterial infections
• Failure to thrive
• Boney deformity - extramedullary haemopoeisis
• Hepatosplenomegaly - due to haemolysis
• Osteopenia

Question 9

Why do individuals with thalassemia get bony deformities?

Answer 9

Chipmunk Facies

Extramedullary haematopoiesis (EMH) is the cause of the facies in this setting.

This leads to decreased normal haemoglobin synthesis and increased red blood cell destruction. To compensate for the low Hb, the bone marrow increases activity (hyperplasia) and haematopoiesis also takes place outside the bone marrow.

Question 10

What are the most commonly affected bones in thalassemia (for bony deformity)?

Answer 10

• Skull
• Facial bone
• Ribs
• Limbs
• Extremities
• Spine

Question 11

What investigations might you do for someone who you suspected had thalassemia?

Answer 11

• Bloods - FBC, Ferritin, Serum Iron, TIBC
• Blood film - Hypochromic, microcytic cells + target cells + nucleated RBCs
• X-ray - characteristic ‘hair on end’ appearance of bony trabeculation as a result of expansion of the bone marrow into cortical bone
• Haemoglobin assays - HbF increased

Question 12

How would you manage someone with Thalassemia?

Answer 12

• Long-term folic acid
• Chronic transfusion support - 4-6 weekly
• Iron chelator
• Ascorbic acid
• Splenectomy
• Marrow transplant

Question 13

Why are iron chelators given in thalassemia?

Answer 13

Desferrioxamine

To prevent iron overload

Question 14

Why is ascorbic acid given in thalassemia?

Answer 14

It increases the urinary excretion of iron in response to desferrioxamine

Question 15

What are effects of iron overload?

Answer 15

Transfusion haemosiderosis

• Damage
  
  • Endocrine glands
  • Liver
  • Pancreas
  • Myocardium